Pharmacokinetics of progesterone in lactating dairy cows: Gaining some insights into the metabolism from kinetic modeling

Autores
Turino, Ludmila Noelia; Mariano, Rodolfo Nicolás; Cabrera, Maria Ines; Scándolo, Daniel E.; Maciel, Martín G.; Grau, Ricardo José Antonio
Año de publicación
2010
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Progesterone pharmacokinetics were analyzed for plasma hormone concentrations ranging from linear to saturated metabolism in lactating Holstein cows with differing daily milk yields. The adequacy of 2-coupled first-order (bi-exponential equation), hyperbolic (Michaelis-Menten equation), and sigmoidal (Hill equation) kinetic models to describe the experimental progesterone pharmacokinetic profiles was examined on a statistical basis. After nonlinear regression andstatistical analysis of the data-fitting capability, a simple one-compartment model based on Hill equation proved to be most adequate. This model indicates an enzyme-catalyzed metabolism of progesterone involving cooperative substrate-binding sites, resulting from allosteric effects that yield a sigmoidal saturation rate curve. Kinetic parameters were estimated for 2 groups of lactating Holstein cows with different daily milk yields. We found, for the first time, a remarkable quantitative agreement of the Hill coefficient value with that reported in pharmacokinetic studies involving cytochrome P450, family 3, subfamily A (CYP3A)-mediated reactions in other mammals, humans included. It seems that positive cooperativity makes enzymes much more sensitive to plasma progesterone concentration, and their activities can undergo significant changes in a narrow range of concentration as characteristic of sigmoidal behavior. Therefore, the values of classical pharmacokinetic parameters, such as the elimination constant, half-life, and clearance rate, were found to be highly dependent on the plasma progesterone concentration.
Fil: Turino, Ludmila Noelia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Desarrollo Tecnológico para la Industria Química. Universidad Nacional del Litoral. Instituto de Desarrollo Tecnológico para la Industria Química; Argentina
Fil: Mariano, Rodolfo Nicolás. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Desarrollo Tecnológico para la Industria Química. Universidad Nacional del Litoral. Instituto de Desarrollo Tecnológico para la Industria Química; Argentina
Fil: Cabrera, Maria Ines. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Desarrollo Tecnológico para la Industria Química. Universidad Nacional del Litoral. Instituto de Desarrollo Tecnológico para la Industria Química; Argentina
Fil: Scándolo, Daniel E.. Instituto Nacional de Tecnologia Agropecuaria. Centro Regional Santa Fe. Estacion Experimental Agropecuaria Rafaela. Agencia de Extension Rural Rafaela; Argentina
Fil: Maciel, Martín G.. Instituto Nacional de Tecnologia Agropecuaria. Centro Regional Santa Fe. Estacion Experimental Agropecuaria Rafaela. Agencia de Extension Rural Rafaela; Argentina
Fil: Grau, Ricardo José Antonio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Desarrollo Tecnológico para la Industria Química. Universidad Nacional del Litoral. Instituto de Desarrollo Tecnológico para la Industria Química; Argentina
Materia
Progesterone
Pharmacokinetics
Dairy Cows
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/246262
Acceder
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network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Pharmacokinetics of progesterone in lactating dairy cows: Gaining some insights into the metabolism from kinetic modelingTurino, Ludmila NoeliaMariano, Rodolfo NicolásCabrera, Maria InesScándolo, Daniel E.Maciel, Martín G.Grau, Ricardo José AntonioProgesteronePharmacokineticsDairy Cowshttps://purl.org/becyt/ford/4.2https://purl.org/becyt/ford/4Progesterone pharmacokinetics were analyzed for plasma hormone concentrations ranging from linear to saturated metabolism in lactating Holstein cows with differing daily milk yields. The adequacy of 2-coupled first-order (bi-exponential equation), hyperbolic (Michaelis-Menten equation), and sigmoidal (Hill equation) kinetic models to describe the experimental progesterone pharmacokinetic profiles was examined on a statistical basis. After nonlinear regression andstatistical analysis of the data-fitting capability, a simple one-compartment model based on Hill equation proved to be most adequate. This model indicates an enzyme-catalyzed metabolism of progesterone involving cooperative substrate-binding sites, resulting from allosteric effects that yield a sigmoidal saturation rate curve. Kinetic parameters were estimated for 2 groups of lactating Holstein cows with different daily milk yields. We found, for the first time, a remarkable quantitative agreement of the Hill coefficient value with that reported in pharmacokinetic studies involving cytochrome P450, family 3, subfamily A (CYP3A)-mediated reactions in other mammals, humans included. It seems that positive cooperativity makes enzymes much more sensitive to plasma progesterone concentration, and their activities can undergo significant changes in a narrow range of concentration as characteristic of sigmoidal behavior. Therefore, the values of classical pharmacokinetic parameters, such as the elimination constant, half-life, and clearance rate, were found to be highly dependent on the plasma progesterone concentration.Fil: Turino, Ludmila Noelia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Desarrollo Tecnológico para la Industria Química. Universidad Nacional del Litoral. Instituto de Desarrollo Tecnológico para la Industria Química; ArgentinaFil: Mariano, Rodolfo Nicolás. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Desarrollo Tecnológico para la Industria Química. Universidad Nacional del Litoral. Instituto de Desarrollo Tecnológico para la Industria Química; ArgentinaFil: Cabrera, Maria Ines. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Desarrollo Tecnológico para la Industria Química. Universidad Nacional del Litoral. Instituto de Desarrollo Tecnológico para la Industria Química; ArgentinaFil: Scándolo, Daniel E.. Instituto Nacional de Tecnologia Agropecuaria. Centro Regional Santa Fe. Estacion Experimental Agropecuaria Rafaela. Agencia de Extension Rural Rafaela; ArgentinaFil: Maciel, Martín G.. Instituto Nacional de Tecnologia Agropecuaria. Centro Regional Santa Fe. Estacion Experimental Agropecuaria Rafaela. Agencia de Extension Rural Rafaela; ArgentinaFil: Grau, Ricardo José Antonio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Desarrollo Tecnológico para la Industria Química. Universidad Nacional del Litoral. Instituto de Desarrollo Tecnológico para la Industria Química; ArgentinaAmerican Dairy Science Association2010-01info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/246262Turino, Ludmila Noelia; Mariano, Rodolfo Nicolás; Cabrera, Maria Ines; Scándolo, Daniel E.; Maciel, Martín G.; et al.; Pharmacokinetics of progesterone in lactating dairy cows: Gaining some insights into the metabolism from kinetic modeling; American Dairy Science Association; Journal of Dairy Science; 93; 3; 1-2010; 988-9990022-0302CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.3168/jds.2009-2519info:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/pii/S0022030210000664info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-11-05T10:02:57Zoai:ri.conicet.gov.ar:11336/246262instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-11-05 10:02:57.424CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Pharmacokinetics of progesterone in lactating dairy cows: Gaining some insights into the metabolism from kinetic modeling
title Pharmacokinetics of progesterone in lactating dairy cows: Gaining some insights into the metabolism from kinetic modeling
spellingShingle Pharmacokinetics of progesterone in lactating dairy cows: Gaining some insights into the metabolism from kinetic modeling
Turino, Ludmila Noelia
Progesterone
Pharmacokinetics
Dairy Cows
title_short Pharmacokinetics of progesterone in lactating dairy cows: Gaining some insights into the metabolism from kinetic modeling
title_full Pharmacokinetics of progesterone in lactating dairy cows: Gaining some insights into the metabolism from kinetic modeling
title_fullStr Pharmacokinetics of progesterone in lactating dairy cows: Gaining some insights into the metabolism from kinetic modeling
title_full_unstemmed Pharmacokinetics of progesterone in lactating dairy cows: Gaining some insights into the metabolism from kinetic modeling
title_sort Pharmacokinetics of progesterone in lactating dairy cows: Gaining some insights into the metabolism from kinetic modeling
dc.creator.none.fl_str_mv Turino, Ludmila Noelia
Mariano, Rodolfo Nicolás
Cabrera, Maria Ines
Scándolo, Daniel E.
Maciel, Martín G.
Grau, Ricardo José Antonio
author Turino, Ludmila Noelia
author_facet Turino, Ludmila Noelia
Mariano, Rodolfo Nicolás
Cabrera, Maria Ines
Scándolo, Daniel E.
Maciel, Martín G.
Grau, Ricardo José Antonio
author_role author
author2 Mariano, Rodolfo Nicolás
Cabrera, Maria Ines
Scándolo, Daniel E.
Maciel, Martín G.
Grau, Ricardo José Antonio
author2_role author
author
author
author
author
dc.subject.none.fl_str_mv Progesterone
Pharmacokinetics
Dairy Cows
topic Progesterone
Pharmacokinetics
Dairy Cows
purl_subject.fl_str_mv https://purl.org/becyt/ford/4.2
https://purl.org/becyt/ford/4
dc.description.none.fl_txt_mv Progesterone pharmacokinetics were analyzed for plasma hormone concentrations ranging from linear to saturated metabolism in lactating Holstein cows with differing daily milk yields. The adequacy of 2-coupled first-order (bi-exponential equation), hyperbolic (Michaelis-Menten equation), and sigmoidal (Hill equation) kinetic models to describe the experimental progesterone pharmacokinetic profiles was examined on a statistical basis. After nonlinear regression andstatistical analysis of the data-fitting capability, a simple one-compartment model based on Hill equation proved to be most adequate. This model indicates an enzyme-catalyzed metabolism of progesterone involving cooperative substrate-binding sites, resulting from allosteric effects that yield a sigmoidal saturation rate curve. Kinetic parameters were estimated for 2 groups of lactating Holstein cows with different daily milk yields. We found, for the first time, a remarkable quantitative agreement of the Hill coefficient value with that reported in pharmacokinetic studies involving cytochrome P450, family 3, subfamily A (CYP3A)-mediated reactions in other mammals, humans included. It seems that positive cooperativity makes enzymes much more sensitive to plasma progesterone concentration, and their activities can undergo significant changes in a narrow range of concentration as characteristic of sigmoidal behavior. Therefore, the values of classical pharmacokinetic parameters, such as the elimination constant, half-life, and clearance rate, were found to be highly dependent on the plasma progesterone concentration.
Fil: Turino, Ludmila Noelia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Desarrollo Tecnológico para la Industria Química. Universidad Nacional del Litoral. Instituto de Desarrollo Tecnológico para la Industria Química; Argentina
Fil: Mariano, Rodolfo Nicolás. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Desarrollo Tecnológico para la Industria Química. Universidad Nacional del Litoral. Instituto de Desarrollo Tecnológico para la Industria Química; Argentina
Fil: Cabrera, Maria Ines. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Desarrollo Tecnológico para la Industria Química. Universidad Nacional del Litoral. Instituto de Desarrollo Tecnológico para la Industria Química; Argentina
Fil: Scándolo, Daniel E.. Instituto Nacional de Tecnologia Agropecuaria. Centro Regional Santa Fe. Estacion Experimental Agropecuaria Rafaela. Agencia de Extension Rural Rafaela; Argentina
Fil: Maciel, Martín G.. Instituto Nacional de Tecnologia Agropecuaria. Centro Regional Santa Fe. Estacion Experimental Agropecuaria Rafaela. Agencia de Extension Rural Rafaela; Argentina
Fil: Grau, Ricardo José Antonio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Desarrollo Tecnológico para la Industria Química. Universidad Nacional del Litoral. Instituto de Desarrollo Tecnológico para la Industria Química; Argentina
description Progesterone pharmacokinetics were analyzed for plasma hormone concentrations ranging from linear to saturated metabolism in lactating Holstein cows with differing daily milk yields. The adequacy of 2-coupled first-order (bi-exponential equation), hyperbolic (Michaelis-Menten equation), and sigmoidal (Hill equation) kinetic models to describe the experimental progesterone pharmacokinetic profiles was examined on a statistical basis. After nonlinear regression andstatistical analysis of the data-fitting capability, a simple one-compartment model based on Hill equation proved to be most adequate. This model indicates an enzyme-catalyzed metabolism of progesterone involving cooperative substrate-binding sites, resulting from allosteric effects that yield a sigmoidal saturation rate curve. Kinetic parameters were estimated for 2 groups of lactating Holstein cows with different daily milk yields. We found, for the first time, a remarkable quantitative agreement of the Hill coefficient value with that reported in pharmacokinetic studies involving cytochrome P450, family 3, subfamily A (CYP3A)-mediated reactions in other mammals, humans included. It seems that positive cooperativity makes enzymes much more sensitive to plasma progesterone concentration, and their activities can undergo significant changes in a narrow range of concentration as characteristic of sigmoidal behavior. Therefore, the values of classical pharmacokinetic parameters, such as the elimination constant, half-life, and clearance rate, were found to be highly dependent on the plasma progesterone concentration.
publishDate 2010
dc.date.none.fl_str_mv 2010-01
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/246262
Turino, Ludmila Noelia; Mariano, Rodolfo Nicolás; Cabrera, Maria Ines; Scándolo, Daniel E.; Maciel, Martín G.; et al.; Pharmacokinetics of progesterone in lactating dairy cows: Gaining some insights into the metabolism from kinetic modeling; American Dairy Science Association; Journal of Dairy Science; 93; 3; 1-2010; 988-999
0022-0302
CONICET Digital
CONICET
url http://hdl.handle.net/11336/246262
identifier_str_mv Turino, Ludmila Noelia; Mariano, Rodolfo Nicolás; Cabrera, Maria Ines; Scándolo, Daniel E.; Maciel, Martín G.; et al.; Pharmacokinetics of progesterone in lactating dairy cows: Gaining some insights into the metabolism from kinetic modeling; American Dairy Science Association; Journal of Dairy Science; 93; 3; 1-2010; 988-999
0022-0302
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.3168/jds.2009-2519
info:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/pii/S0022030210000664
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv American Dairy Science Association
publisher.none.fl_str_mv American Dairy Science Association
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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score 13.084122

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